The research proposal seeks to identify possible regulatory DNA regions responsible for alpha globin gene expression and for the coordinate regulation of alpha and non-alpha globin gene expression. Persons with deletion and nondeletion forms of alpha-thalassemia will be identified by restriction endonuclease mapping. Abnormal alpha globin gene complexes including flanking DNA regions from patients with the deletion and nondeletion varieties of Hb H disease will be cloned by recombinant DNA techniques and analyzed by restriction endonuclease mapping, contact filter hybridization, and heteroduplex mapping. By comparing the fine structure of abnormal alpha globin gene complexes in which expression is altered to normals, critical differences in DNA structure will be sought which may represent DNA regions responsible for the control of alpha globin gene expression. In addition, DNA regions of similarity between alpha and non-alpha globin gene complexes will be examined for their possible role in the coordinate expression of nonlinked globin genes.